Stem Cell Transplant in Patients With Thalassemia - Full Text View

Purpose

The major goal of this study is to determine the amount of liver fibrosis and iron storage in a patient's liver before transplant (bone marrow/stem cell) from an unrelated donor. Too much liver damage could mean that there will be more problems with the transplant, and that medications that can further damage the liver need to be adjusted.

Condition	Intervention	Phase
Thalassemia	Drug: Busulfan Drug: Fludarabine Drug: Campath 1H Drug: Cyclophosphamide Drug: MESNA Procedure: Bone marrow or stem cell infusion	Phase II

Genetics Home Reference related topics:

beta thalassemia

MedlinePlus related topics:

Thalassemia

ChemIDplus related topics:

Mesna Cyclophosphamide Fludarabine Fludarabine monophosphate Alemtuzumab Campath Busulfan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study

Official Title:	Pilot Study of Allogeneic Stem Cell Transplantation From Unrelated Donors for Patients With Severe Homozygous Beta 0/+ Thalassemia or Severe Variants of Beta 0/+ Thalassemia

Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:

Evaluate engraftment [ Time Frame: 30 days post transplant ] [ Designated as safety issue: Yes ]
To evaluate the occurrence of transient and stable mixed hematopoietic chimerism (HC) after unrelated donor SCT and its effect on the recurrence of clinically measurable thalassemia. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
To measure hematopoietic and immune reconstitution and assess the effects on infectious complications. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
toxicities [ Time Frame: +100 days transplant ] [ Designated as safety issue: Yes ]
loss of chimerism [ Time Frame: 2 years post transplant ] [ Designated as safety issue: Yes ]
GVHD [ Time Frame: 2 years post transplant ] [ Designated as safety issue: Yes ]
morbidity and mortality post transplant [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	15
Study Start Date:	February 2004
Estimated Study Completion Date:	February 2011
Estimated Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms

Assigned Interventions

Patients: Experimental

Patients with diagnosis of severe (transfusion-dependent) homozygous b0/+-thalassemia or severe variants of b0/+-thalassemia requiring chronic transfusion therapy and iron chelating agents.

Drug: Busulfan

4.0 mg/kg/day divided into four doses daily for four days; total dose = 16 mg/kg

days -9 through -6

Drug: Fludarabine

30mg/m2 day -5 through day -2

Drug: Campath 1H

per institutional guidelines days -5 through -2

Drug: Cyclophosphamide

50mg/kg days -5 through -2

Drug: MESNA

10mg/kg x 5 days -5 through -2

Procedure: Bone marrow or stem cell infusion

day +2 To ensure the probability for bone marrow engraftment, 4 x 108 nucleated cells/kg patient weight or 5 x 106/kg of CD34+cells/kg patient weight if the product is mobilized peripheral blood, will be the target to be obtained from the unrelated donor.

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Eligibility

Ages Eligible for Study:	up to 64 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with documented diagnosis of severe (transfusion-dependent) homozygous b0/+-thalassemia or severe variants of b0/+-thalassemia requiring chronic transfusion therapy and iron chelating agents who fulfill the following conditions:

Patient does not have an HLA genotype identical donor available and has a 5/6 or 6/6 matched unrelated donor or a 5/6 matched related donor available.
Must be the between 1 and 16 yrs of age (all Pesaro risk groups).
Patients older than 17 yrs of age must be in Pesaro Risk Class 2 or lower (see Appendix B)
Women of childbearing potential must have a negative pregnancy test
Documentation of compliance with iron chelation, absence or presence of hepatomegaly, and presence or absence of hepatic fibrosis prior to transplant (criteria for the Pesaro Risk Classification). This information will be obtained by history, physical exam and interpretation of liver biopsy results.
Documentation of awareness of alternative treatment options.

Exclusion Criteria:

Biopsy-proven chronic active hepatitis or fibrosis with portal bridging
Creatinine clearance <35 ml/min/1.73 M2
Severe cardiac dysfunction defined as shortening fraction <25%
HIV infection
Inadequate intellectual capacity to give informed consent (in the case of minors, this criteria must be fulfilled by the legal guardian)
Be pregnant, lactating or unwilling to use appropriate birth control

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00578292

Contacts


Contact: Kathryn Suet Wa Leung, MD	832-822-4200	kleung@bcm.edu

Contact: Kathryn Suet Wa Leung, MD	832-822-4200	kleung@bcm.tmc.edu

Locations


United States, Texas
	Texas Children's Hospital	Recruiting
	Houston, Texas, United States, 77030
	Contact: Marlen Dinu 832-824-4881 mxdinu@txccc.org
	Contact: Kathryn Suet Wa Leung, MD 832-822-4200 kleung@bcm.tmc.edu
	Principal Investigator: Kathryn Suet Wa Leung, MD

Sponsors and Collaborators

Baylor College of Medicine

Investigators


Principal Investigator:	Kathryn Suet Wa Leung, MD	Baylor College of Medicine/Texas Children's Hospital

More Information

Responsible Party:	Baylor College of Medicine/Texas Children's Hospital ( Kathryn Suet Wa Leung )
Study ID Numbers:	14539, THALLO
First Received:	December 19, 2007
Last Updated:	February 7, 2008
ClinicalTrials.gov Identifier:	NCT00578292
Health Authority:	United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:

transfusion-dependent

homozygous b0/+-thalassemia

severe variants of b0/+-thalassemia

chronic transfusion therapy

iron chelating agents

severe

transfusion-dependent homozygous b0/+-thalassemia or severe variants of b0/+-thalassemia

Study placed in the following topic categories:

Hematologic Diseases

Anemia

Anemia, Hemolytic

Cyclophosphamide

Fludarabine monophosphate

Thalassemia

Anemia, Hemolytic, Congenital

Genetic Diseases, Inborn

Busulfan

Hemoglobinopathies

Alemtuzumab

Fludarabine

Hemoglobinopathy

Mesna

Iron

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action

Immunologic Factors

Antineoplastic Agents

Therapeutic Uses

Physiological Effects of Drugs

Myeloablative Agonists

Antineoplastic Agents, Alkylating

Antirheumatic Agents

Alkylating Agents

Immunosuppressive Agents

Pharmacologic Actions

ClinicalTrials.gov processed this record on October 10, 2008

Sponsored by:	Baylor College of Medicine
Information provided by:	Baylor College of Medicine
ClinicalTrials.gov Identifier:	NCT00578292